Hypomethylating agent and venetoclax with FLT3 inhibitor "triplet" therapy in older/unfit patients with FLT3 mutated AML.
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
02 05 2022
02 05 2022
Historique:
received:
22
02
2022
accepted:
07
04
2022
revised:
30
03
2022
entrez:
2
5
2022
pubmed:
3
5
2022
medline:
6
5
2022
Statut:
epublish
Résumé
In older/unfit newly diagnosed patients with FLT3 mutated acute myeloid leukemia (AML), lower intensity chemotherapy (LIC) in combination with either a FLT3 inhibitor or with venetoclax results in poor overall survival (median 8 to 12.5 months). We performed a retrospective analysis of 87 newly diagnosed FLT3 mutated AML patients treated on triplet (LIC + FLT3 inhibitor + Venetoclax, [N = 27]) and doublet (LIC + FLT3 inhibitor, [N = 60]) regimens at our institution. Data were collected from prospective clinical trials in 75% (N = 65) and 25% (N = 22) who received the same treatment regimens outside of a clinical trial. Triplet therapy was associated with significantly higher rates of complete remission (CR) (67% versus 32%, P = 0.002), CR/CRi (93% versus 70%, P = 0.02), FLT3-PCR negativity (96% versus 54%, P < 0.01), and flow-cytometry negativity (83% versus 38%, P < 0.01) than doublets. At the end of the first cycle, the median time to ANC > 0.5 (40 versus 21 days, P = 0.15) and platelet > 50 K (29 versus 25 days, P = 0.6) among responders was numerically longer with triplets, but 60-day mortality was similar (7% v 10%). With a median follow-up of 24 months (median 12 months for triplet arm, and 63 months for doublet arm), patients receiving a triplet regimen had a longer median overall survival (not reached versus 9.5 months, P < 0.01). LIC combined with FLT3 inhibitor and venetoclax (triplet) may be an effective frontline regimen for older/unfit FLT3 mutated AML that should be further validated prospectively.
Identifiants
pubmed: 35501304
doi: 10.1038/s41408-022-00670-0
pii: 10.1038/s41408-022-00670-0
pmc: PMC9061716
doi:
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
Protein Kinase Inhibitors
0
Sulfonamides
0
FLT3 protein, human
EC 2.7.10.1
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
venetoclax
N54AIC43PW
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
77Subventions
Organisme : NCI NIH HHS
ID : T32 CA009666
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA100632
Pays : United States
Informations de copyright
© 2022. The Author(s).
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